Lessons learned and implications of early therapies for coronavirus disease in a territorial service centre in the Calabria region: a retrospective study.

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited. METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients. RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events. CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.

Utility, acceptability and applicability of a nucleic acid amplification test in comparison with a syndromic approach in the management of sexually transmitted diseases at Mulago National Referral Hospital in Uganda (ASTRHA): protocol for an open-label, randomised controlled trial.

INTRODUCTION: Sexually transmitted diseases (STDs) are a major cause of long-term disability. Urethral discharge syndrome (UDS), abnormal vaginal discharge (AVD) and genital ulcer disease (GUD) are very common in low-income and middle-income countries (LMICs), where, due to lack of resources, these infections are managed according to a syndromic approach. Although microbiological diagnosis using nuclear acid amplification tests (NAAT) is already a standard to prescribe targeted treatments in industrialised countries, no randomised clinical trials have been conducted to evaluate clinical usefulness and acceptability of NAAT in comparison with syndromic approach in LMICs. The results of this study could inform diagnostic guidelines since they may suggest an update of the current recommendation if microbiological diagnosis using NAAT in the management of STD is demonstrated to be both useful and acceptable in an LMIC context. METHODS AND ANALYSIS: The primary objective of this randomised, open-label trial is to evaluate the clinical usefulness of a NAAT and its acceptability in comparison with a clinical syndromic approach and to explore whether this test could replace the syndromic approach in the management of STDs at a national referral hospital in Uganda. 220 patients presenting to the STD clinic at Mulago Hospital in Kampala, Uganda with AVD, UDS or GUD will be randomised to either standard of care (syndromic management) or NAAT-based treatment with a 1:1 ratio. All the patients will be asked to return after 2 or 3 weeks for a control visit. Primary outcome will be therapeutic appropriateness. ETHICS AND DISSEMINATION: This trial was approved by the Mulago Hospital Research and Ethical Committee (MHREC2023-97) and the Uganda National Council for Science and Technology (HS31000ES). Patients will give informed consent to participate before taking part in the study. Results will be published in peer-reviewed journals in open-access formats and data made available in anonymised form. TRIAL REGISTRATION NUMBER: NCT05994495.

Interleukin-62/lymphocyte as a proposed predictive index for COVID-19 patients treated with monoclonal antibodies.

In a convenience sample of 93 patients treated with monoclonal antibodies (moAbs) against SARS-CoV-2, the interleukin-62/lymphocyte count ratio (IL-62/LC) was able to predict clinical worsening both in early stages of COVID-19 and in oxygen-requiring patients. Moreover, we analysed 18 most at-risk patients with asymptomatic or mild disease treated with both moAbs and antiviral treatment and found that only 2 had clinical progression, while patients with a similar risk were reported to have an unfavourable outcome in most cases from recent data. In only one of our 18 patients, clinical progression was attributable to COVID-19, and in the other cases, clinical progression was observed despite IL-62/LC being above the risk cut-off. In conclusion, IL-62/LC may be a valuable method to identify patients requiring more aggressive treatments both in earlier and later stages of the disease; however, most at-risk patients can be protected from clinical worsening by combining moAbs and antivirals, even if levels of the IL-62/LC biomarker are lower than the risk cut-off.

Evolution of in-hospital patient characteristics and predictors of death in the COVID-19 pandemic across four waves: are they moving targets with implications for patient care?

Objectives: The aim of this work was to study characteristics, outcomes and predictors of all-cause death in inpatients with SARS-CoV-2 infection across the pandemic waves in one large teaching hospital in Italy to optimize disease management. Methods: All patients with SARS-CoV-2 infection admitted to our center from March 2020 to June 2022 were included in this retrospective observational cohort study. Both descriptive and regression tree analyses were applied to identify factors influencing all-cause mortality. Results: 527 patients were included in the study (65.3% with moderate and 34.7% with severe COVID-19). Significant evolutions of patient characteristics were found, and mortality increased in the last wave with respect to the third wave notwithstanding vaccination. Regression tree analysis showed that in-patients with severe COVID-19 had the greatest mortality across all waves, especially the older adults, while prognosis depended on the pandemic waves in patients with moderate COVID-19: during the first wave, dyspnea was the main predictor, while chronic kidney disease emerged as determinant factor afterwards. Conclusion: Patients with severe COVID-19, especially the older adults during all waves, as well as those with moderate COVID-19 and concomitant chronic kidney disease during the most recent waves require more attention for monitoring and care. Therefore, our study drives attention towards the importance of co-morbidities and their clinical impact in patients with COVID-19 admitted to hospital, indicating that the healthcare system should adapt to the evolving features of the epidemic.

Bacterial Ventilator-Associated Pneumonia in COVID-19 Patients: Data from the Second and Third Waves of the Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, many patients requiring invasive mechanical ventilation were admitted to intensive care units (ICU) for COVID-19-related severe respiratory failure. As a matter of fact, ICU admission and invasive ventilation increased the risk of ventilator-associated pneumonia (VAP), which is associated with high mortality rate and a considerable burden on length of ICU stay and healthcare costs. The objective of this review was to evaluate data about VAP in COVID-19 patients admitted to ICU that developed VAP, including their etiology (limiting to bacteria), clinical characteristics, and outcomes. The analysis was limited to the most recent waves of the epidemic. The main conclusions of this review are the following: (i) P. aeruginosa, Enterobacterales, and S. aureus are more frequently involved as etiology of VAP; (ii) obesity is an important risk factor for the development of VAP; and (iii) data are still scarce and increasing efforts should be put in place to optimize the clinical management and preventative strategies for this complex and life-threatening disease.

Orthopedic Device-Related Infections Due to Emerging Pathogens Diagnosed by a Combination of Microbiological Approaches: Case Series and Literature Review.

Orthopedic and trauma device-related infections (ODRI) due to high virulence microorganisms are a devastating complication after orthopedic surgery. Coagulase-negative Staphylococci (CoNS) are mainly involved but commensal bacteria, located in human mucous membranes, are emerging pathogens in ODRI. Currently, bacterial culture is the gold standard for ODRI but the diagnostic process remains time consuming and laborious. We evaluated a combination of microbiological approaches in the diagnosis of emerging pathogens involved in ODRI. We analyzed two synovial fluids, five tissue samples and five surgical wound swabs from two different patients with ODRI, attending the Department of Orthopedic and Trauma Surgery of Mater Domini Teaching Hospital, Catanzaro, Italy. Identification was carried out with a combination of microbiological approaches (culture, mass spectrometry and 16s rRNA gene sequencing). We demonstrated the importance of a combination of microbiological approaches for the diagnosis of emerging pathogens in ODRI, because the low number of cases in the literature makes it very difficult to formulate guidelines for the management of patients.

Clinical Characteristics and Outcome of Hospitalized COVID-19 Patients Treated with Standard Dose of Dexamethasone or High Dose of Methylprednisolone.

The hyperinflammatory phase represents the main cause for the clinical worsening of acute respiratory distress syndrome (ARDS) in Coronavirus disease 2019 (COVID-19), leading to the hypothesis that steroid therapy could be a mainstream treatment in COVID-19 patients. This is an observational study including all consecutive patients admitted to two Italian University Hospitals for COVID-19 from March 2020 to December 2021. The aim of this study was to describe clinical characteristics and outcome parameters of hospitalized COVID-19 patients treated with dexamethasone 6 mg once daily (standard-dose group) or methylprednisolone 40 mg twice daily (high-dose group). The primary outcome was the impact of these different steroid treatments on 30-day mortality. During the study period, 990 patients were evaluated: 695 (70.2%) receiving standard dosage of dexamethasone and 295 (29.8%) receiving a high dose of methylprednisolone. Cox regression analysis showed that chronic obstructive pulmonary disease (HR 1.98, CI95% 1.34−9.81, p = 0.002), chronic kidney disease (HR 5.21, CI95% 1.48−22.23, p = 0.001), oncologic disease (HR 2.81, CI95% 1.45−19.8, p = 0.005) and high-flow nasal cannula, continuous positive airway pressure or non-invasive ventilation oxygen therapy (HR 61.1, CI95% 5.12−511.1, p < 0.001) were independently associated with 30-day mortality; conversely, high-dose steroid therapy was associated with survival (HR 0.42, CI95% 0.38−0.86, p = 0.002) at 30 days. Kaplan−Meier curves for 30-day survival displayed a statistically significant better survival rate in patients treated with high-dose steroid therapy (p = 0.018). The results of this study highlighted that the use of high-dose methylprednisolone, compared to dexamethasone 6 mg once daily, in hospitalized patients with COVID-19 may be associated with a significant reduction in mortality.